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Background: Obstructive sleep apnoea (OSA) can cause left atrial (LA) and left ventricular (LV) remodelling, which is linked to atrial fibrillation (AF). Whether continuous positive airway pressure (CPAP) can reverse LA and LV remodelling in patients with OSA and paroxysmal AF (PAF) has yet to be studied. We assessed the impact of CPAP treatment on LA and LV size and function in patients with OSA and PAF before and after catheter ablation., Methods: In a randomised controlled trial, we screened patients with PAF for OSA. We enrolled patients with an Apnoea-Hypopnoea Index ≥15/hour. The burden of AF was monitored by an implantable loop recorder in all patients. Patients were then randomised to CPAP treatment or standard care. Transthoracic echocardiography was performed at baseline and after 6 and 12 months to assess LV and LA function and remodelling with advanced echocardiographic imaging techniques., Results: We enrolled 109 patients (63±7 years, body mass index 29.6±4.3, 76% men). 83 patients were scheduled for pulmonary vein isolation (PVI) and 26 for clinical follow-up only. 55 patients were randomised to CPAP and 54 to standard care. The burden of AF decreased significantly in patients who underwent PVI irrespective of treatment with CPAP (p for difference ≤0.001). Patients in the study group had LV ejection fraction (LVEF) and LV global longitudinal strain (GLS) within the normal range, increased LA Volume Index (LAVI), LA volume (by speckle tracking) and decreased LA reservoir strain at baseline. We did not observe any improvement in LVEF, GLS, LAVI, LA volume or LA reservoir strain in either group during the 12 months of follow-up., Conclusions: In patients with PAF and OSA, treatment with CPAP was not associated with reverse LA remodelling within 12 months of follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Studies on the effect of insomnia on atrial fibrillation risk in the general population are limited, therefore we investigated the association between insomnia and the risk of atrial fibrillation in a large-scale population-based study with valid atrial fibrillation measure. A total of 33,983 participants (55% women) reported their insomnia symptoms in the third wave of the HUNT study (between 2006 and 2008) in Norway, and they were followed for their first atrial fibrillation diagnosis until 2020 using hospital registers. Atrial fibrillation diagnoses were validated by physicians based on medical records and electrocardiograms. Insomnia symptoms were assessed by four questions, and analysed both individually and as cumulative symptoms. Cox regression, adjusted for age, sex, social and marital status, working in shiftwork, alcohol consumption, smoking, physical activity, body mass index, systolic blood pressure, and symptoms of anxiety and depression, was conducted. Overall, 1592 atrial fibrillation cases were identified during the follow-up and 31.6% of individuals reported at least one insomnia symptom. In our analysis, we did not detect meaningful associations between insomnia symptoms and the risk of atrial fibrillation. In conclusion, in this population there was no evidence for an association between insomnia symptoms and the risk of subsequent atrial fibrillation., (© 2024 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Aims: Although parity, infertility, and age at first birth are important for later development of cardiovascular disease, research on their association with atrial fibrillation (AF) is limited., Methods and Results: We linked data from the population-based HUNT study and the Medical Birth Registry of Norway (MBRN) and validated medical records from local hospitals. A total of 24 015 women aged 45 years or older were followed for verified incident AF. Parity and age at first birth were retrieved from the MBRN or from self-reported questionnaires in the HUNT study. A history of infertility was self-reported on the HUNT questionnaire. Cox proportional hazards models were used to calculate hazard ratios (HRs) for the multivariable-adjusted associations of parity, infertility, and age at first birth with risk of AF. During a median follow-up of 12.8 years, 1448 (6.0%) participants developed AF. Women with higher parity (four or more births vs. two births) were at 21% higher risk of AF [HR 1.21, 95% confidence interval (CI) 1.05-1.39]. A history of infertility was also associated with the risk of AF (HR 1.20, 95% CI 1.02-1.42). Among parous women, younger age at first birth (<20 vs. 20-29 years) was associated with a 20% higher risk of AF (HR 1.20, 95% CI 1.03-1.40)., Conclusion: Women with four or more births, or a history of infertility, or younger age at first birth have approximately a 20% higher risk of AF among women over 45 years old., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Catheter ablation in patients with atrial fibrillation is associated with a transient increase in thromboembolic risk and adequate anticoagulation is highly important. When patients are anticoagulated with apixaban, monitoring of plasma concentrations of the drug is not routinely performed. This study aimed to assess the influence of clinical patient characteristics, concomitant drug treatment and self-reported adherence on apixaban concentrations, and to describe the intra- and inter-individual variability in apixaban concentrations in this group of patients. Method Apixaban concentrations from 141 patients were measured in plasma one week before ablation and two, six and ten weeks after ablation, employing ultra-high performance liquid chromatography coupled with tandem mass spectrometry. In samples not obtained at trough, apixaban concentrations were adjusted to trough levels. Self-reported adherence was registered by means of the 8-item Morisky Medication Adherence Scale before and after ablation., Results: There were statistically significant, positive correlations between apixaban concentrations and increased age, female sex, lower glomerular filtration rate, higher CHA2DS2-VASc score, use of cytochrome P450 3A4 and/or p-glycoprotein inhibitors, and use of amiodarone. Self-reported adherence was generally high. The mean intra-individual and inter-individual coefficients of variation were 29% and 49%, respectively., Conclusion: In patients undergoing catheter ablation for atrial fibrillation, age, sex, renal function, interacting drugs and cerebrovascular risk profile were all associated with altered plasma apixaban concentration. In this group of patients with a generally high self-reported adherence, intra-individual variability was modest, but the inter-individual variability was substantial, and similar to those previously reported in other patient apixaban-treated populations. If a therapeutic concentration range is established, there might be a need for a more flexible approach to apixaban dosing, guided by therapeutic drug monitoring., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aakerøy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Age at menarche, reproductive lifespan, and age at menopause are associated with several cardiovascular diseases, but their relationship with atrial fibrillation (AF) is uncertain., Methods: We linked information on all women who participated in the third survey of the population-based, longitudinal HUNT study in Norway with medical records from all local hospitals. A total of 14,632 women aged 60 or more were followed for validated incident AF. We retrieved age at menarche and age at menopause from the HUNT questionnaires. Reproductive lifespan was defined as the difference between age at menarche and age at menopause. We used Cox proportional hazards regression models to assess associations between AF and age at menarche, reproductive lifespan, and age at menopause., Results: During a median follow-up of 8.17 years (136,494 person-years), 1217 (8.3 %) participants developed AF. In multivariable-adjusted analyses, we observed no associations between early or late age at menarche and AF (hazard ratios (HRs): <12 years: 0.85 [95 % confidence interval (CI), 0.65-1.12]; ≥16 years: 0.99 [95 % CI, 0.80-1.24] compared to those who attained menarche at 13-14 years). The HR for a reproductive lifespan shorter than 30 years was 0.91 [95 % CI, 0.72-1.15] compared to 34-37 years. Likewise, there was no clear association between premature or early age at menopause and AF (HRs: <40 years: 1.21 [95 % CI, 0.83-1.75]; 40-44 years: 0.97 [95 % CI, 0.77-1.22] compared to 50-54 years)., Conclusions: In this population of women aged 60 years and over, the risk of AF was not associated with age at menarche, reproductive lifespan, or age at menopause., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Gastroesophageal reflux disease (GERD) may influence the risk of atrial fibrillation (AF). We investigated the association between symptoms of GERD and AF in the Trøndelag Health Study (HUNT)., Methods: The study cohort comprised 34,120 adult men and women initially free of AF with information on GERD symptoms. Participants were followed from the baseline clinical examination (1 October 2006 to 30 June 2008) to March 31, 2018., Results: During a median follow-up of 8.9 years, 1,221 cases of AF were diagnosed. When looking at the whole population, participants with much GERD symptoms did not have an increased risk of AF (HR: 1.01; CI: 95%, 0.82 to 1.24) while participants with little GERD symptoms had a 14% lower risk of AF compared those with no GERD symptoms (HR: 0.86; CI: 95%, 0.76 to 0.97). Among younger participants (<40 years of age), the risk of AF had a trend towards increased risk with increasing symptom load of GERD (little GERD symptoms, HR: 3.09; CI: 95%, 0.74 to 12.94 and much GERD symptoms, HR: 5.40; 95% CI: 0.82 to 35.58). Among older participants (≥65 years of age), we saw a slightly reduced risk of AF in participants with little symptoms (HR: 0.84; CI: 0.72 to 0.97) and no association among those with much GERD symptoms (HR: 1.06; 95% CI: 0.82 to 1.36)., Conclusion: We did not find support for a clinically important association between symptoms of GERD and AF across all age groups but for some younger people, GERD might play a role in the development of AF. However, our estimates for this age group were very imprecise and larger studies including younger individuals are warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Drca et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Data from some population-based studies have indicated an increased risk of atrial fibrillation (AF) among patients with migraine, particularly among individuals with migraine with aura. The present study aimed to assess the association between primary headache disorders and AF., Methods: In a population-based 9-year follow-up design, we evaluated the questionnaire-based headache diagnosis, migraine and tension-type headache (TTH) included, collected in the Trøndelag Health Study (HUNT3) conducted in 2006-2008, and the subsequent risk of AF in the period until December 2015. The population at risk consisted of 39,340 individuals ≥20 years without AF at HUNT3 baseline who answered headache questionnaire during HUNT3. The prospective association was evaluated by multivariable Cox proportional hazard models with 95% confidence intervals (CIs)., Results: Among the 39,340 participants, 1524 (3.8%) developed AF during the 9-year follow up, whereof 91% of these were ≥55 years. In the multivariable analyses, adjusting for known confounders, we did not find any association between migraine or TTH and risk of AF. The adjusted hazard ratios (HRs) were respectively 0.84 (95% CI = 0.64-1.11) for migraine, 1.16 (95% CI = 0.86-1.27) for TTH and 1.04 (95% CI = 0.86-1.27) for unclassified headache. However, in sensitivity analyses of individuals aged ≥55 years, a lower risk of AF was found for migraine (HR = 0.53; 95% CI = 0.39-0.73)., Conclusions: In this large population-based study, no increased risk of AF was found among individuals with migraine or TTH at baseline. Indeed, among individuals aged ≥55 years, migraine was associated with a lower risk for AF., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Ventricular arrhythmias contribute significantly to cardiovascular mortality, with coronary artery disease as the predominant underlying cause. Understanding the mechanisms of arrhythmogenesis is essential to identify proarrhythmic factors and develop novel approaches for antiarrhythmic prophylaxis and treatment. Animal models are vital in basic research on cardiac arrhythmias, encompassing molecular, cellular, ex vivo whole heart, and in vivo models. Most studies use either in vivo protocols lacking important information on clinical relevance or exclusively ex vivo protocols, thereby missing the opportunity to explore underlying mechanisms. Consequently, interpretation may be difficult due to dissimilarities in animal models, interventions, and individual properties across animals. Moreover, proarrhythmic effects observed in vivo are often not replicated in corresponding ex vivo preparations during mechanistic studies. We have established a protocol to perform both an in vivo and ex vivo electrophysiological characterization in an arrhythmogenic rat model with heart failure following myocardial infarction. The same animal is followed throughout the experiment. In vivo methods involve intracardiac programmed electrical stimulation and external defibrillation to terminate sustained ventricular arrhythmia. Ex vivo methods conducted on the Langendorff-perfused heart include an electrophysiological study with optical mapping of regional action potentials, conduction velocities, and dispersion of electrophysiological properties. By exploring the retention of the in vivo proarrhythmic phenotype ex vivo, we aim to examine whether the subsequent ex vivo detailed measurements are relevant to in vivo pathological behavior. This protocol can enhance greater understanding of cardiac arrhythmias by providing a standardized, yet adaptable model for evaluating arrhythmogenicity or antiarrhythmic interventions in cardiac diseases. NEW & NOTEWORTHY Rodent models are widely used in arrhythmia research. However, most studies do not standardize clinically relevant in vivo and ex vivo techniques to support their conclusions. Here, we present a comprehensive electrophysiological protocol in an arrhythmogenic rat model, connecting in vivo and ex vivo programmed electrical stimulation with optical mapping. By establishing this protocol, we aim to facilitate the adoption of a standardized model for investigating arrhythmias, enhancing research rigor and comparability in this field.

Endurance athletes have a high prevalence of atrial fibrillation (AF), probably caused by exercise-induced cardiac remodelling. Athletes diagnosed with AF are often advised to reduce the intensity and amount of training but the efficacy of this intervention has not been investigated in endurance athletes with AF. Effects of detraining in endurance athletes with atrial fibrillation is a two-arm international multicentre randomised (1:1) controlled trial on the effects of a period of training adaption on AF burden in endurance athletes with paroxysmal AF. One-hundred-and-twenty endurance athletes diagnosed with paroxysmal AF are randomised to a 16-week period of intervention (training adaption) or a control group. We define training adaption as training with a heart rate (HR) not exceeding 75% of the individual maximum HR (HRmax), and total duration of weekly training not exceeding 80% of the self-reported average before the study. The control group is instructed to uphold training intensity including sessions with HR ≥85% of HRmax. AF burden is monitored with insertable cardiac monitors, and training intensity with HR chest-straps and connected sports watches. The primary endpoint, AF burden, will be calculated as the cumulative duration of all AF episodes lasting ≥30sec divided by total duration of monitoring. Secondary endpoints include number of AF episodes, adherence to training adaption, exercise capacity, AF symptoms and health-related quality of life, echocardiographic signs of cardiac remodelling and risk of cardiac arrhythmias related to upholding training intensity., Trial Registration Number: NCT04991337., Study Protocol Version: 4.7 (Date 9 March 2023)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Pulseless electrical activity (PEA) is commonly observed in in-hospital cardiac arrest (IHCA). Universally available ECG characteristics such as QRS duration (QRSd) and heart rate (HR) may develop differently in patients who obtain ROSC or not. The aim of this study was to assess prospectively how QRSd and HR as biomarkers predict the immediate outcome of patients with PEA., Method: We investigated 327 episodes of IHCA in 298 patients at two US and one Norwegian hospital. We assessed the ECG in 559 segments of PEA nested within episodes, measuring QRSd and HR during pauses of compressions, and noted the clinical state that immediately followed PEA. We investigated the development of HR, QRSd, and transitions to ROSC or no-ROSC (VF/VT, asystole or death) in a joint longitudinal and competing risks statistical model., Results: Higher HR, and a rising HR, reflect a higher transition intensity ("hazard") to ROSC (p < 0.001), but HR was not associated with the transition intensity to no-ROSC. A lower QRSd and a shrinking QRSd reflect an increased transition intensity to ROSC (p = 0.023) and a reduced transition intensity to no-ROSC (p = 0.002)., Conclusion: HR and QRSd convey information of the immediateoutcome during resuscitation from PEA. These universally available and promising biomarkers may guide the emergency team in tailoring individual treatment., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Whether treatment with continuous positive airway pressure (CPAP) reduces AF recurrence after catheter ablation with pulmonary vein isolation (PVI) is unknown., Objective: The purpose of this study was to assess the effect of CPAP treatment on the recurrence and burden of AF after PVI in patients with OSA., Methods: We randomized patients with paroxysmal AF and an apnea-hypopnea index (AHI) ≥15 events/hour to treatment with CPAP or standard care. Heart rhythm was monitored by an implantable loop recorder. AF recurrence after PVI was defined as any episode of AF lasting >2 minutes after a 3-month blanking period., Results: PVI was performed in 83 patients. Thirty-seven patients were randomized to CPAP treatment and 46 patients to standard care. The AHI was reduced from 26.7 ± 14 events/hour to 1.7 ± 1.3 events/hour at follow-up in the CPAP group (P = .001). A total of 57% of patients in both the CPAP group and the standard care group had at least 1 episode of AF 3-12 months after PVI (P for difference = 1). AF burden after ablation was reduced in both groups, with no between-group difference (P = .69)., Conclusion: In patients with paroxysmal AF and OSA, treatment with CPAP did not further reduce the risk of AF recurrence after ablation. PVI considerably reduced the burden of AF in OSA patients, without any difference between groups., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)